m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00360)
Target Name Programmed cell death 1 ligand 1 (CD274/PD-L1)
Gene Name CD274
Chromosomal Location 9p24.1
Family immunoglobulin superfamily; BTN/MOG family
Function
Plays a critical role in induction and maintenance of immune tolerance to self. As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response . Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10); The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival. The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function (By similarity). The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (By similarity).
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Gene ID 29126
Uniprot ID
PD1L1_HUMAN
HGNC ID
HGNC:17635
Ensembl Gene ID
ENSG00000120217
KEGG ID
hsa:29126
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
CD274 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Methyltransferase-like 3 (METTL3) [WRITER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line LX2 cell line Homo sapiens
Treatment: shMETTL3 LX2 cells
Control: shLuc LX2 cells
 GSE207909
Regulation
logFC: -1.82E+00
p-value: 4.68E-65
More Results Click to View More RNA-seq Results
Representative RIP-seq result supporting the interaction between CD274 and the regulator
Cell Line MDA-MB-231 Homo sapiens
Regulation logFC: 7.97E+00 GSE60213
In total 4 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary METTL3 intensified the metastasis and proliferation of OSCC by modulating the m6A amounts of PRMT5 and Programmed cell death 1 ligand 1 (CD274/PD-L1).
Target Regulation Up regulation
Responsed Disease Oral squamous cell carcinoma ICD-11: 2B6E.0
 Disease Info 
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
In-vitro Model SCC-9 Tongue squamous cell carcinoma Homo sapiens CVCL_1685
SCC-4 Tongue squamous cell carcinoma Homo sapiens CVCL_1684
SCC-25 Tongue squamous cell carcinoma Homo sapiens CVCL_1682
CAL-27 Tongue squamous cell carcinoma Homo sapiens CVCL_1107
In-vivo Model Six-week-old nude mice were randomly divided into two groups (three mice per group) and cultured with continuous access to sterile food and water in pathogen-free sterile conditions. To establish the OSCC xenograft model, we subcutaneously injected 5 × 106 SCC-9 cells stably transfected with METTL3 shRNA or sh-NC vectors into nude mice.
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
Central carbon metabolism in cancer hsa05230
PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Experiment 3 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary Programmed cell death 1 ligand 1 (CD274/PD-L1) was a downstream target of METTL3-mediated m6A modification in breast cancer cells. METTL3-mediated PD-L1 mRNA activation was m6A-IGF2BP3-dependent. PD-L1 expression was also positively correlated with METTL3 and IGF2BP3 expression in breast cancer tissues.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Tumor immune escape
In-vitro Model SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-10A Normal Homo sapiens CVCL_0598
HCC38 Breast ductal carcinoma Homo sapiens CVCL_1267
4T1 Normal Mus musculus CVCL_0125
In-vivo Model For subcutaneous xenograft experiments in B-NDG mice, approximately 1 × 106 MDA-MB-231 and there was subcutaneous injection of the cells that resuspended in 100 uL PBS into the left flank of the mice and were divided into 11 groups randomly (each containing 5 mice). After the treatment Atezolizumab (Selleck, Shanghai, China) or corresponding iso control antibody (Selleck, Shanghai, China) was injected intratumorally on day 3, 6, 9, 12, 15 post-MDA-MB-231 inoculations, and 5 × 106 cytokine-induced killer (CIK) cells were injected in the tail vein on day 7, 14, 21.
Experiment 4 Reporting the m6A Methylation Regulator of This Target Gene [4]
Response Summary METTL3 was essential for bladder cancer cells to resist the cytotoxicity of CD8+ T cells by regulating Programmed cell death 1 ligand 1 (CD274/PD-L1) expression. Additionally, JNK signaling contributed to tumor immune escape in a METTL3-dependent manner both in vitro and in vivo.
Target Regulation Up regulation
Responsed Disease Bladder cancer ICD-11: 2C94
 Disease Info 
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
In-vitro Model UM-UC-3 Bladder carcinoma Homo sapiens CVCL_1783
T24 Bladder carcinoma Homo sapiens CVCL_0554
SV-HUC-1 Normal Homo sapiens CVCL_3798
J82 Bladder carcinoma Homo sapiens CVCL_0359
5637 Bladder carcinoma Homo sapiens CVCL_0126
In-vivo Model male C57BL/6J mice (6 weeks old) were given drinking water containing 0.05% (w/v) BBN (TCI, catalog no. B0938) for 20 weeks. After the BBN administration, mice were given normal drinking water and injected with 10% DMSO (as a control) or 20 mg/kg SP600125 (Selleck, catalog no. 129-56-6) i.p. every 3 days. After seven injections, mice were euthanized for tissue retrieval. For the bladder cancer cell-derived xenograft mouse model, male C57BL/6J mice (6 weeks old) were injected subcutaneously with 1 × 106 MB49 cells. One week after bladder cancer cell injection, 10% DMSO or 20 mg/kg SP600125 were injected i.p. every 3 days.
Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by FTO
Cell Line 253J cell line Homo sapiens
Treatment: siFTO 253J cells
Control: 253J cells
 GSE150239
Regulation
logFC: 3.22E+00
p-value: 3.45E-05
More Results Click to View More RNA-seq Results
In total 2 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [5]
Response Summary Arecoline-induced FTO promotes the stability and expression levels of Programmed cell death 1 ligand 1 (CD274/PD-L1) transcripts through mediating m6A modification and MYC activity, respectively. PD-L1 upregulation confers superior cell proliferation, migration, and resistance to T-cell killing to OSCC cells.
Target Regulation Up regulation
Responsed Disease Oral squamous cell carcinoma ICD-11: 2B6E.0
 Disease Info 
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Experiment 2 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
Central carbon metabolism in cancer hsa05230
PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
RNA demethylase ALKBH5 (ALKBH5) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line 143B cell line Homo sapiens
Treatment: siALKBH5 transfected 143B cells
Control: siControl 143B cells
 GSE154528
Regulation
logFC: 2.95E+00
p-value: 3.40E-21
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [6]
Response Summary ALKBH5 as an important m6A demethylase that orchestrates Programmed cell death 1 ligand 1 (CD274/PD-L1) expression in intrahepatic cholangiocarcinoma (ICC).
Target Regulation Up regulation
Responsed Disease Intrahepatic cholangiocarcinoma ICD-11: 2C12.10
 Disease Info 
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
In-vitro Model TFK-1 Cholangiocarcinoma Homo sapiens CVCL_2214
RBE Intrahepatic cholangiocarcinoma Homo sapiens CVCL_4896
LIPF178c (LIPF178c human bile duct cancer cells from China Center for Type Culture Collection (Wuhan, China))
LIPF155c (LIPF155c human bile duct cancer cells from China Center for Type Culture Collection (Wuhan, China))
LICCF (LICCF human intrahepatic bile duct cancer cell line from China Center for Type Culture Collection (Wuhan, China))
HCCC-9810 Intrahepatic cholangiocarcinoma Homo sapiens CVCL_6908
In-vivo Model ICC tumor cells (LIPF178c-shCtrl/shALKBH5) of 5 × 106 were injected into the right flank of NCG mice. Tumor volume was calculated by the formula: volume = ab2/2 (a, the longer axis; b, the shorter axis). T-cell killing assay in vitro was conducted as previously reported (20). PBMCs from healthy donors were activated and expanded as described above. The day before tumor cell injection, PBMC (i.v. 1 × 107 cells) was adoptively transferred to NCG mice via the tail vein. At the end, the PBMC was isolated and subjected to flow cytometry for detecting T-cell percentage.
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary Programmed cell death 1 ligand 1 (CD274/PD-L1) was a downstream target of METTL3-mediated m6A modification in breast cancer cells. METTL3-mediated PD-L1 mRNA activation was m6A-IGF2BP3-dependent. PD-L1 expression was also positively correlated with METTL3 and IGF2BP3 expression in breast cancer tissues.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Tumor immune escape
In-vitro Model SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-10A Normal Homo sapiens CVCL_0598
HCC38 Breast ductal carcinoma Homo sapiens CVCL_1267
4T1 Normal Mus musculus CVCL_0125
In-vivo Model For subcutaneous xenograft experiments in B-NDG mice, approximately 1 × 106 MDA-MB-231 and there was subcutaneous injection of the cells that resuspended in 100 uL PBS into the left flank of the mice and were divided into 11 groups randomly (each containing 5 mice). After the treatment Atezolizumab (Selleck, Shanghai, China) or corresponding iso control antibody (Selleck, Shanghai, China) was injected intratumorally on day 3, 6, 9, 12, 15 post-MDA-MB-231 inoculations, and 5 × 106 cytokine-induced killer (CIK) cells were injected in the tail vein on day 7, 14, 21.
YTH domain-containing family protein 1 (YTHDF1) [READER]
 Regulator Info 
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease Non-small-cell lung carcinoma ICD-11: 2C25.Y
 Disease Info 
Pathway Response p53 signaling pathway hsa04115
Central carbon metabolism in cancer hsa05230
PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Head and neck squamous carcinoma [ICD-11: 2B6E]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [5]
Response Summary Arecoline-induced FTO promotes the stability and expression levels of Programmed cell death 1 ligand 1 (CD274/PD-L1) transcripts through mediating m6A modification and MYC activity, respectively. PD-L1 upregulation confers superior cell proliferation, migration, and resistance to T-cell killing to OSCC cells.
Responsed Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Experiment 2 Reporting the m6A-centered Disease Response [1]
Response Summary METTL3 intensified the metastasis and proliferation of OSCC by modulating the m6A amounts of PRMT5 and Programmed cell death 1 ligand 1 (CD274/PD-L1).
Responsed Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
In-vitro Model SCC-9 Tongue squamous cell carcinoma Homo sapiens CVCL_1685
SCC-4 Tongue squamous cell carcinoma Homo sapiens CVCL_1684
SCC-25 Tongue squamous cell carcinoma Homo sapiens CVCL_1682
CAL-27 Tongue squamous cell carcinoma Homo sapiens CVCL_1107
In-vivo Model Six-week-old nude mice were randomly divided into two groups (three mice per group) and cultured with continuous access to sterile food and water in pathogen-free sterile conditions. To establish the OSCC xenograft model, we subcutaneously injected 5 × 106 SCC-9 cells stably transfected with METTL3 shRNA or sh-NC vectors into nude mice.
Colorectal cancer [ICD-11: 2B91]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response []
Response Summary WM_Score correlated highly with the regulation of transcription and post-transcriptional events contributing to the development of colorectal cancer. In response to anti-cancer drugs, WM_Score highly negatively correlated (drug sensitive) with drugs which targeted oncogenic related pathways, such as MAPK, EGFR, and mTOR signaling pathways, positively correlated (drug resistance) with drugs which targeted in apoptosis and cell cycle. Importantly, the WM_Score was associated with the therapeutic efficacy of Programmed cell death 1 ligand 1 (CD274/PD-L1) blockade, suggesting that the development of potential drugs targeting these "writers" to aid the clinical benefits of immunotherapy.
Responsed Disease Colorectal cancer [ICD-11: 2B91]
Pathway Response MAPK signaling pathway hsa04010
VEGF signaling pathway hsa04370
mTOR signaling pathway hsa04150
PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Cell apoptosis
Liver cancer [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [6]
Response Summary ALKBH5 as an important m6A demethylase that orchestrates Programmed cell death 1 ligand 1 (CD274/PD-L1) expression in intrahepatic cholangiocarcinoma (ICC).
Responsed Disease Intrahepatic cholangiocarcinoma [ICD-11: 2C12.10]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
In-vitro Model TFK-1 Cholangiocarcinoma Homo sapiens CVCL_2214
RBE Intrahepatic cholangiocarcinoma Homo sapiens CVCL_4896
LIPF178c (LIPF178c human bile duct cancer cells from China Center for Type Culture Collection (Wuhan, China))
LIPF155c (LIPF155c human bile duct cancer cells from China Center for Type Culture Collection (Wuhan, China))
LICCF (LICCF human intrahepatic bile duct cancer cell line from China Center for Type Culture Collection (Wuhan, China))
HCCC-9810 Intrahepatic cholangiocarcinoma Homo sapiens CVCL_6908
In-vivo Model ICC tumor cells (LIPF178c-shCtrl/shALKBH5) of 5 × 106 were injected into the right flank of NCG mice. Tumor volume was calculated by the formula: volume = ab2/2 (a, the longer axis; b, the shorter axis). T-cell killing assay in vitro was conducted as previously reported (20). PBMCs from healthy donors were activated and expanded as described above. The day before tumor cell injection, PBMC (i.v. 1 × 107 cells) was adoptively transferred to NCG mice via the tail vein. At the end, the PBMC was isolated and subjected to flow cytometry for detecting T-cell percentage.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 3 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Pathway Response p53 signaling pathway hsa04115
Central carbon metabolism in cancer hsa05230
PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Experiment 2 Reporting the m6A-centered Disease Response [2]
Response Summary This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Pathway Response p53 signaling pathway hsa04115
Central carbon metabolism in cancer hsa05230
PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Experiment 3 Reporting the m6A-centered Disease Response [2]
Response Summary This study revealed that m6A methylation is closely related to the poor prognosis of non-small cell lung cancer patients via interference with the TIME, which suggests that m6A plays a role in optimizing individualized immunotherapy management and improving prognosis. The expression levels of METTL3, FTO and YTHDF1 in non-small cell lung cancer were changed. Patients in Cluster 1 had lower immunoscores, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, and shorter overall survival compared to patients in Cluster 2. The hallmarks of the Myelocytomatosis viral oncogene (MYC) targets, E2 transcription Factor (E2F) targets were significantly enriched.
Responsed Disease Non-small-cell lung carcinoma [ICD-11: 2C25.Y]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
 Regulator Info 
Pathway Response p53 signaling pathway hsa04115
Central carbon metabolism in cancer hsa05230
PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary Programmed cell death 1 ligand 1 (CD274/PD-L1) was a downstream target of METTL3-mediated m6A modification in breast cancer cells. METTL3-mediated PD-L1 mRNA activation was m6A-IGF2BP3-dependent. PD-L1 expression was also positively correlated with METTL3 and IGF2BP3 expression in breast cancer tissues.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Tumor immune escape
In-vitro Model SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-10A Normal Homo sapiens CVCL_0598
HCC38 Breast ductal carcinoma Homo sapiens CVCL_1267
4T1 Normal Mus musculus CVCL_0125
In-vivo Model For subcutaneous xenograft experiments in B-NDG mice, approximately 1 × 106 MDA-MB-231 and there was subcutaneous injection of the cells that resuspended in 100 uL PBS into the left flank of the mice and were divided into 11 groups randomly (each containing 5 mice). After the treatment Atezolizumab (Selleck, Shanghai, China) or corresponding iso control antibody (Selleck, Shanghai, China) was injected intratumorally on day 3, 6, 9, 12, 15 post-MDA-MB-231 inoculations, and 5 × 106 cytokine-induced killer (CIK) cells were injected in the tail vein on day 7, 14, 21.
Experiment 2 Reporting the m6A-centered Disease Response [3]
Response Summary Programmed cell death 1 ligand 1 (CD274/PD-L1) was a downstream target of METTL3-mediated m6A modification in breast cancer cells. METTL3-mediated PD-L1 mRNA activation was m6A-IGF2BP3-dependent. PD-L1 expression was also positively correlated with METTL3 and IGF2BP3 expression in breast cancer tissues.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Tumor immune escape
In-vitro Model SK-BR-3 Breast adenocarcinoma Homo sapiens CVCL_0033
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-10A Normal Homo sapiens CVCL_0598
HCC38 Breast ductal carcinoma Homo sapiens CVCL_1267
4T1 Normal Mus musculus CVCL_0125
In-vivo Model For subcutaneous xenograft experiments in B-NDG mice, approximately 1 × 106 MDA-MB-231 and there was subcutaneous injection of the cells that resuspended in 100 uL PBS into the left flank of the mice and were divided into 11 groups randomly (each containing 5 mice). After the treatment Atezolizumab (Selleck, Shanghai, China) or corresponding iso control antibody (Selleck, Shanghai, China) was injected intratumorally on day 3, 6, 9, 12, 15 post-MDA-MB-231 inoculations, and 5 × 106 cytokine-induced killer (CIK) cells were injected in the tail vein on day 7, 14, 21.
Bladder cancer [ICD-11: 2C94]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response []
Response Summary m6A-related prognostic lncRNA signature serves as a crucial mediator of the immune microenvironment in bladder cancer, representing promising therapeutic targets for improving immunotherapeutic efficacy. Cluster 1 was significantly correlated with poor prognosis, advanced clinical stage, higher Programmed cell death 1 ligand 1 (CD274/PD-L1) expression, a higher ESTIMATEScore and immuneScore, and distinct immune cell infiltration.
Responsed Disease Bladder cancer [ICD-11: 2C94]
Pathway Response JAK-STAT signaling pathway hsa04630
PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
Cell Process Cell apoptosis
Experiment 2 Reporting the m6A-centered Disease Response [4]
Response Summary METTL3 was essential for bladder cancer cells to resist the cytotoxicity of CD8+ T cells by regulating Programmed cell death 1 ligand 1 (CD274/PD-L1) expression. Additionally, JNK signaling contributed to tumor immune escape in a METTL3-dependent manner both in vitro and in vivo.
Responsed Disease Bladder cancer [ICD-11: 2C94]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
Target Regulation Up regulation
Pathway Response PD-L1 expression and PD-1 checkpoint pathway in cancer hsa05235
In-vitro Model UM-UC-3 Bladder carcinoma Homo sapiens CVCL_1783
T24 Bladder carcinoma Homo sapiens CVCL_0554
SV-HUC-1 Normal Homo sapiens CVCL_3798
J82 Bladder carcinoma Homo sapiens CVCL_0359
5637 Bladder carcinoma Homo sapiens CVCL_0126
In-vivo Model male C57BL/6J mice (6 weeks old) were given drinking water containing 0.05% (w/v) BBN (TCI, catalog no. B0938) for 20 weeks. After the BBN administration, mice were given normal drinking water and injected with 10% DMSO (as a control) or 20 mg/kg SP600125 (Selleck, catalog no. 129-56-6) i.p. every 3 days. After seven injections, mice were euthanized for tissue retrieval. For the bladder cancer cell-derived xenograft mouse model, male C57BL/6J mice (6 weeks old) were injected subcutaneously with 1 × 106 MB49 cells. One week after bladder cancer cell injection, 10% DMSO or 20 mg/kg SP600125 were injected i.p. every 3 days.
References
Ref 1 METTL3 Intensifies the Progress of Oral Squamous Cell Carcinoma via Modulating the m6A Amount of PRMT5 and PD-L1. J Immunol Res. 2021 Aug 23;2021:6149558. doi: 10.1155/2021/6149558. eCollection 2021.
Ref 2 Correlation of m6A methylation with immune infiltrates and poor prognosis in non-small cell lung cancer via a comprehensive analysis of RNA expression profiles. Ann Transl Med. 2021 Sep;9(18):1465. doi: 10.21037/atm-21-4248.
Ref 3 METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N(6)-methyladenosine modification of PD-L1 mRNA in breast cancer. Mol Cancer. 2022 Feb 23;21(1):60. doi: 10.1186/s12943-021-01447-y.
Ref 4 JNK Signaling Promotes Bladder Cancer Immune Escape by Regulating METTL3-Mediated m6A Modification of PD-L1 mRNA. Cancer Res. 2022 May 3;82(9):1789-1802. doi: 10.1158/0008-5472.CAN-21-1323.
Ref 5 Fat mass and obesity-associated protein regulates arecoline-exposed oral cancer immune response through programmed cell death-ligand 1. Cancer Sci. 2022 Mar 15. doi: 10.1111/cas.15332. Online ahead of print.
Ref 6 M(6)A Demethylase ALKBH5 Regulates PD-L1 Expression and Tumor Immunoenvironment in Intrahepatic Cholangiocarcinoma. Cancer Res. 2021 Sep 15;81(18):4778-4793. doi: 10.1158/0008-5472.CAN-21-0468. Epub 2021 Jul 23.